Journal
DIABETES CARE
Volume 44, Issue 6, Pages 1402-1409Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc20-2089
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Funding
- European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) [609020]
- Norwegian Diabetes Centre
- Swedish Heart-Lung Foundation
- Crafoordska Stiftelsen
- Direktor Albert Pahlssons Stiftelse
- Oslo Diabetes Research Centre
- Lund University Diabetes Center (Swedish Research Council)
- Lund University Diabetes Center (Strategic Research Area EXODIAB) [2009-1039]
- Lund University Diabetes Center (Linnaeus grant) [349-2006-23]
- Lund University Diabetes Center (Swedish Foundation for Strategic Research) [IRC15-006]
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In type 1 diabetes, autoantibodies against AGE-modified apoB100 are inversely associated with coronary atherosclerosis and proliferative retinopathy, indicating a vascular protective effect of these autoantibodies.
OBJECTIVE Methylglyoxal (MGO), a reactive aldehyde forming advanced glycation end products (AGEs), is increased in diabetes and recognized by the immune system, resulting in anti-AGE-specific autoantibodies. The association of these immune responses with macro- and microvascular complications in type 1 diabetes remains unclarified. We investigated associations between MGO-modified apolipoprotein B100 (apoB100) and apoB100 peptide 5 (MGO-p5) autoantibodies and coronary atherosclerosis and retinopathy in type 1 diabetes. RESEARCH DESIGN AND METHODS IgM and IgG against MGO-apoB100 and MGO-p5 were measured by ELISA in plasma from 103 subjects with type 1 diabetes and 63 control subjects (Dialong study) and in a replication cohort of 27 subjects with type 1 diabetes (Oslo study). Coronary atherosclerosis was assessed by computed tomography coronary angiography or intravascular ultrasound. Retinopathy was classified by retinal photos. RESULTS MGO-apoB100 IgM and MGO-p5 IgM levels were higher in subjects with diabetes with no coronary artery stenosis compared with subjects with significant stenosis (median [interquartile range]: 96.2 arbitrary units [AU] [71-126.8] vs. 54 AU [36.1-85.4], P = 0.003 for MGO-apoB100; and 77.4 AU [58-106] vs. 36.9 AU [28.9-57.4], P = 0.005 for MGO-p5). MGO-apoB100 IgM and MGO-p5 IgM were associated with less severe coronary stenosis after adjusting for confounders (odds ratio 0.2 [95% CI 0.05-0.6], P = 0.01; and 0.22 [0.06-0.75], P = 0.02). The inverse association of MGO-p5 IgM and coronary stenosis was confirmed in the replication cohort. Subjects with proliferative retinopathy had significantly lower MGO-apoB100 IgM and MGO-p5 IgM than those with background retinopathy. CONCLUSIONS Autoantibodies against AGE-modified apoB100 are inversely associated with coronary atherosclerosis and proliferative retinopathy, suggesting vascular protective effects of these autoantibodies in type 1 diabetes.
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